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Cancer Research and Treatment > Accepted Articles
doi: https://doi.org/10.4143/crt.2023.999    [Accepted]
Tandem High-dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors
Hana Lim1 , Minji Im2 , Eun Seop Seo1, Hee Won Cho1, Hee Young Ju1, Keon Hee Yoo1, Sung Yoon Cho1, Jong-Won Kim3, Do Hoon Lim4, Ki Woong Sung1 , Ji Won Lee1
1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Department of Pediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
3Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
4Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence  Ki Woong Sung ,Tel: 82-2-3410-3529, Fax: 82-2-3410-0043, Email: kwsped@skku.edu
Ji Won Lee ,Tel: 82-2-3410-0659, Fax: 82-2-3410-0043, Email: leejw.lee@samsung.com
Received: September 1, 2023;  Accepted: November 23, 2023.  Published online: November 24, 2023.
*Hana Lim and Minji Im contributed equally to this work.
This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT).
Materials and Methods
Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk.
A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680 ± 0.002% and 10.193 ± 0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively.
The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.
Key words: Secondary malignant neoplasms, pediatric solid tumor, Radiation, high-dose chemotherapy
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